Cross-study analyses of the ropeginterferon alfa-2b effect on phlebotomy in low- and high-risk patients with polycythemia vera.

Therapeutic phlebotomy maintains hematocrit (Hct) <45% in patients with polycythemia vera (PV) and reduces thrombotic risks. However, frequent phlebotomy can induce iron deficiency. Ropeginterferon alfa-2b (ropeg) is a new-generation interferon therapy that induces durable complete hematologic and molecular responses through reduction of the Janus kinase 2 (JAK2)-mutated clone. Two dosing regimens have been investigated: the FDA-approved slow-titration regimen and a higher initial dose and accelerated titration (HIDAT) regimen. A cross-analysis of three prospective trials showed that ropeg achieved sustained Hct control and reduction of phlebotomy dependence in PV patients, including high-risk and hydroxyurea-resistant/intolerant patients. In exploratory cross-study comparisons, the HIDAT regimen was associated with more rapid phlebotomy-free Hct response rates, lower mean annualized phlebotomy frequency, higher overall hematologic response rates and deeper JAK2V617F allele burden reduction than slow titration. Both regimens were safe and well tolerated. Ropeg treatment provides durable Hct control and phlebotomy-independence in a broad PV population, including high-risk patients.